Wells Receives ASBMB-Merck Award

BY ANGELA HOPP AND NICK ZAGORSKI

James A. Wells, professor and chairman of the department of pharmaceutical chemistry at the University of California, San Francisco, and director of UCSF’s small molecule discovery center, has been named the winner of the 2010 American Society for Biochemistry and Molecular Biology-Merck Award for his pioneering studies in the field of protein engineering.

Wells, who also serves on the ASBMB Council, will present an award lecture, titled “Probing and Controlling Cellular Remodeling Enzymes,” at 2:15 p.m. Monday, April 26, at the 2010 annual meeting in Anaheim, Calif.

Wells integrates multiple disciplines, including biophysics, cell biology, chemical biology, molecular biology, enzymology and proteomics, to design small molecules and proteins that can selectively activate or inhibit cellular processes, such as differentiation and apoptosis. Through those efforts, Wells hopes to better understand how signaling events drive responses, such as cell growth and death, and perhaps discover new drugs to treat diseases like cancer.

Along the way, Wells has developed numerous innovative methodologies to improve protein engineering, molecular screening and pharmaceutical chemistry, including a disulfide-based protein-trapping technology, substrate-assisted catalysis and N-terminomics.

“[Wells] is an exciting and highly creative scientist,” noted Ian A. Wilson, professor of structural biology at The Scripps Research Institute, “and these methods that he has pioneered have been invaluable to countless researchers in a multitude of fields.”

“His unbridled enthusiasm is infectious and ensures his lab is fully regaled with a plethora of ideas,” Wilson continued, “so they can unleash their individual talents to further progress drug discovery, biochemical mechanisms, protein function and understanding of key cellular events that impact human health.”

Wells’ impressive expertise in protein engineering stems from a long and renowned career in the pharmaceutical industry. Before joining UCSF, Wells spent nearly two decades at Genentech Inc., where he was a founding scientist of its protein engineering department. During his time there, Wells produced several key scientific breakthroughs. For example, his group’s work with the protease subtilisin was one of the first instances of scientifically improving upon evolution and nature, as they designed a subtilisin enzyme that was more stable to oxidation, heat and alkali (paving the way for its industrial use in laundry detergents and other household products).

Later, in 1998, Wells founded and served as president and chief scientific officer of Sunesis Pharmaceuticals and helped invent a novel drug-discovery platform called Tethering, which efficiently screens molecules to identify the most potent compounds that block specific protein action.

Prior to that, Wells received his bachelor’s degree in biochemistry from the University of California, Berkeley, in 1973 and his doctorate in biochemistry from Washington State University in 1979 (working with Ralph Yount). He also took on postdoctoral fellowships at both Washington State University and the Stanford University School of Medicine before joining Genentech in 1982.

“Over his career, Wells has made enormous contributions to our understanding of enzyme mechanisms, allostery, protein plasticity, protein-protein interfaces, small molecule discovery, hormone receptor signaling, molecular recognition, protease signaling and apoptosis,” said Molecular and Cellular Proteomics co-editor Alma Burlingame, who is also a professor of chemistry and pharmaceutical chemistry at UCSF. “Not only has his science led to fundamental discoveries, it also produced new products in both the industrial enzyme and pharmaceutical sectors.”

The ASBMB-Merck Award, presented annually, recognizes outstanding research contributions in the fields of biochemistry and molecular biology.

See the December 2008 issue of ASBMB Today to read an ASBMB Roundtable discussion with Wells on improving the global health system.